Tetrahydrofuran → 5-[(Z)-(5-chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide

HRID 1243903Notes

Reaction equation

HRID 1243903 reaction equation
N1([C:6]([C:8]2[C:9]([CH3:16])=[C:10]([CH:14]=O)[NH:11][C:12]=2[CH3:13])=[O:7])C=CN=C1.[NH2:17][CH2:18][C@H:19]([OH:27])[CH2:20][N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.[Cl:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][C:33](=[O:38])[CH2:32]2.C1COCC1>C(N(CC)CC)C>[Cl:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][C:33](=[O:38])/[C:32]/2=[CH:14]\[C:10]1[NH:11][C:12]([CH3:13])=[C:8]([C:6]([NH:17][CH2:18][C@H:19]([OH:27])[CH2:20][N:21]2[CH2:22][CH2:23][O:24][CH2:25][CH2:26]2)=[O:7])[C:9]=1[CH3:16]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 1528015-ChlorooxindoleHCID 1380975(S)-1-Amino-3-morpholinopropan-2-ol2×HCID 219318934-(1H-imidazol-1-ylcarbonyl)-3,5-dimethyl-1H-pyrrole-2-carbaldehyde

Product 1

HCID 591120555-[(Z)-(5-chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamideYield 38.1%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

4-(1H-imidazol-1-ylcarbonyl)-3,5-dimethyl-1H-pyrrole-2-carbaldehyde (6.8 g, 31.3 mmol), (2S)-1-amino-3-morpholin-4-ylpropan-2-ol (10.0 g, 62.5 mmol), 5-chlorooxindole (5.3 g, 31.6 mmol), and THF (100 ml) were mixed and heated to 60° C. After stirring for 68 h at 60° C., triethylamine (14 ml) was added and stirred for 5 h at 60° C. Added 4.6 g of (2S)-1-amino-3-morpholin-4-ylpropan-2-ol, and stirred for 20 h at 60° C. The yellow slurry was cooled to room temperature and filtered. The cake was washed with 2×50 ml THF and dried overnight at 50° C. under house vacuum. 5-[(Z)-(5-chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (5.48 g) was obtained with 38% yield.

Workup

  1. stirringstirred for 5 h at 60° C
  2. stirringstirred for 20 h at 60° C
  3. temperatureThe yellow slurry was cooled to room temperature
  4. filtrationfiltered
  5. washThe cake was washed with 2×50 ml THF
  6. customdried overnight at 50° C. under house vacuum

Sources & evidence

ORD record
ord-e090240b0ed743c8abe3abddc66d3f94
Source dataset
uspto-grants-2006_10
Patent number
US07119209B2

Reaction notes

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